DE 19724458 A1 describes the use of proteolytic enzymes for the improvement of the absorption of pharmaceutical active ingredients.
EP 1302201 A1 describes pharmaceutical compositions improved in peroral absorbability. The composition comprises a drug, an aminoalkyl methacrylate copolymer E and an acidic substance.
EP 1466626 A1 describes medical compositions for improving oral absorption. The aminoalkyl methacrylate copolymer E is described therein as an agent for inhibiting the decomposition of a biological active peptide.
WO2005007139A2 describes an oral multiparticulate pharmaceutical form comprising pellets having a size in the range from 50 to 2500 μm, which are substantially composed of                a) an inner matrix layer comprising an active substance which is a peptide or a protein, including derivatives or conjugates thereof, and is embedded in a matrix of a polymer having a mucoadhesive effect, where the matrix may optionally comprise further pharmaceutically usual excipients,        b) an outer film coating consisting essentially of an anionic polymer or copolymer which may optionally be formulated with pharmaceutically usual excipients, especially plasticizers, characterized in thatthe multiparticulate pharmaceutical form is formulated so that the contained pellets are released in the pH range of the stomach, the outer coating is adjusted through the choice of the anionic polymer or copolymer or its formulation with excipients and its layer thickness such that the coating dissolves in pH ranges from 4.0 to 8.0 in the intestine within 15 to 60 min, so that the active substance-containing, mucoadhesive matrix layer is exposed, and can bind to the intestinal mucosa and release the active substance there, where the polymer having a mucoadhesive effect is chosen so that it exhibits a mucoadhesive effect of ηb=150 to 1000 mPa·s and a water uptake of from 10 to 750% in 15 min in a range of +/−0.5 pH units relative to the pH at which the outer coating starts to dissolve, and the active substance content of the matrix layer is a maximum of 40% by weight of the content of polymer having a mucoadhesive effect.        
It is mentioned that the mucoadhesive matrix layer may contain further excipients such as protease inhibitors, for instance a soybean trypsin inhibitor, or penetration promoters. However it is suggested to use penetration promoters only in combination with high molecular weight (Mw) active ingredients such as proteins with a Mw of 10.000 or more. Protease inhibitors may be used in combination with proteins or peptides with a Mw of 3.000 to 10.000 and stabilizers such as fatty acids or fatty alcohols which form a lipophilic matrix. There are no concrete examples in which protease inhibitors and penetration promoters are combined.
EP 1771157 B1 describes a multiparticle pharmaceutical dosage form for a low-soluble active substances and method for producing said pharmaceutical dosage form.
WO 2006/061069 A1 describes a multiparticle form of administration comprising nucleic acid containing mucoadhesive active ingredients and methods for producing said forms of administration.
The Bowman-Birk inhibitor (BBI) is a well known designation of a family of stable low molecular weight trypsin and chymotrypsin inhibitors found in soybeans and various other seeds, mainly in leguminous seeds and vegetable materials. See for instance U.S. Pat. No. 5,962,414 or U.S. Pat. No. 6,767,564.
U.S. Pat. No. 6,767,564 B2 describes the use bowman birk inhibitor (BBI) for the treatment of multiple sclerosis and other autoimmune diseases such as Guillian Barre Syndrome and rheumatoid arthritis. It is mentioned that orally ingested bowman birk inhibitor is absorbed and has systemic effects. Approximately 50% of the ingested bowman birk inhibitor is absorbed in to the bloodstream. It is further mentioned that bowman birk inhibitor concentrate (BBIC), a soybean derived extract enriched in the protease inhibitor, is reportedly a better inhibitor of human chymases than any other physiologic protease inhibitor described to date.